USPTO Patents Application 10561839

United States Patent and Trademark Ofhce

UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark OtBce

Address: COMMISSIONER FOR PATENTS

APPLICATION NO.

10/561,839

FILING DATE

06/05/2006

FIRST NAMED INVENTOR

Mordechai Deutsch

ATTORNEY DOCKET NO. CONFIRMATION NO.

67801 7590 08/17/2010

MARTIN D. MOYNIHAN d/b/a PRTSI, INC.
P.O. BOX 16446
ARLINGTON, VA 22215

EDWARDS, LYDIAE

PAPER NUMBER

DELIVERY MODE

Please find below and/or attached an Office communication concerning this application or proceeding.

The time period for reply, if any, is set in the attached communication.

PTOL-90A (Rev. 04/07)

KJtSiVrXS nvrliyjts OUff Iff fcff Jr

Application No.

10/561,839

Applicant(s)

DEUTSCH ETAL.

Examiner
LYDIA EDWARDS

Art Unit
1797

- The MAILING DATE of this communication appears on the cover sheet with the correspondence address —
Period for Reply

A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTH(S) OR THIRTY (30) DAYS,
WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.

- Extensions of time may be available under the provisions of 37 CFR 1 .136(a). In no event, however, may a reply be timely filed
after SIX (6) MONTHS from the mailing date of this communication.

- If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.

- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
eamed patent term adjustment. See 37 CFR 1 .704(b).

Status

1 )^ Responsive to communication(s) filed on 07 June 2010 .
2a )^ This action is FINAL. 2b)n This action is non-final.

3) D Since this application is in condition for allowance except for formal matters, prosecution as to the merits is

closed in accordance with the practice under Ex parte Quayle, 1935 CD. 11, 453 O.G. 213.

Disposition of Claims

4) ^ Claim(s) See Continuation Sheet is/are pending in the application.

4a) Of the above claim(s) is/are withdrawn from consideration.

5) n Claim(s) is/are allowed.

6) ^ Claim(s) See Continuation Sheet is/are rejected.
/)□ Claim(s) is/are objected to.

8) 0 Claim(s) are subject to restriction and/or election requirement.

Application Papers

9) 0 The specification is objected to by the Examiner.

10)0 The drawing(s) filed on is/are: a)^ accepted or b)^ objected to by the Examiner.

Applicant may not request that any objection to the drawing(s) be held In abeyance. See 37 CFR 1.85(a).

Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).
1 !)□ The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-152.

Priority under 35 U.S.C. § 119

12)0 Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
a)n All b)n Some * c)^ None of:

1 .□ Certified copies of the priority documents have been received.

2. n Certified copies of the priority documents have been received in Application No. .

3. n Copies of the certified copies of the priority documents have been received in this National Stage

application from the International Bureau (PCT Rule 17.2(a)).
* See the attached detailed Office action for a list of the certified copies not received.

Attach ment(s)

1 ) □ Notice of References Cited (PTO-892) 4) □ Interview Summary (PTO-413)

2) □ Notice of Draftsperson's Patent Drawing Review (PTO-948) Paper No(s)/Mail Date. .

3) ^ Information Disclosure Statement(s) (PTO/SB/08) 5) □ Notice of Informal Patent Application

Paper No(s)/Mail Date See Continuation Sheet . 6) □ Other: .

'TOL-326 (Rev. 08-06) Office Action Summary Part of Paper No./Mail Date 20100814

Continuation Sheet (PTOL-326)

Application No. 10/561,839

Continuation of Disposition of Claims: Claims pending in the application are 1-3,5-

7,12,18,22,27,29,30,42,43,48,49,56,68,74,80,86,90,91,105,109,111,121,130,132,139,145,153,156,178,179,181,186 and
193.

Continuation of Disposition of Claims: Claims rejected are 1-3,5-

7,12,18,22,27,29,30,42,43,48,49,56,68,74,80,86,90,91,105,109,111,121,130,132,139,145,153,156,178,179,181,186 and
193.

Continuation of Attachment(s) 3). Information Disclosure Statement(s) (PTO/SB/08), Paper No(s)/Mail Date :5/1 1/2010,
5/25/2010, 6/6/2010, 6/14/2010 and 6/22/2010.

2

Application/Control Number: 1 0/561 ,839 Page 2

Art Unit: 1797

DETAILED ACTION
Response to Arguments
Applicant's arguments filed 6/7/2010 have been fully considered but they are not
persuasive.

In response to applicant's arguments that Bochner does not disclose, teach, or suggest
that the wells are configured to or formed to inhibit adhesion, the examiner respectfully
disagrees. The wells of Bochner inherently inhibit adhesion. He teaches in each embodiment, the
microorganisms (cells) to be tested are mixed in a suspension comprising a gelling agent, and
then inoculated into a well, compartment, or other receptacle, which contains the biochemical(s)
to be tested, along with a gel-initiating agent such as various cations. Upon contact of the gelling
agent with the gel-initiating agent (e.g., cations), the suspension solidifies to form a viscous
colloid or gel, with the organisms evenly distributed throughout (Col 14, lines 18-25). As
interpreted by the examiner, the cells never actually adhere to and or touch the wall of the well
but instead they remain encapsulated by the gel or the viscous colloid.

Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a
general allegation that the claims define a patentable invention without specifically pointing out
how the language of the claims patentably distinguishes them from the references.

In response to applicant's arguments that Kim does not disclose, teach, or suggest that the
wells are configured to or formed to inhibit adhesion, the examiner respectfully disagrees. Kim
discloses in Paragraph 139 where portions of the surface can be treated, conditioned, or coated
with a substance that resists cell attachment.

Application/Control Number: 1 0/561 ,839 Page 3

Art Unit: 1797

In response to applicant's arguments that Kim does not disclose, teach, or suggest a
surface having protuberances, or of removing cells from a biological sample by contacting the
sample with said surface, the examiner respectfiiUy disagrees. As interpreted by the examiner,
Figure lb discloses protuberances [150 and 160].

Furthermore, Kim discloses wherein the cells are allowed to attach to the support
(surface) [140] and to grow to confluence. The walls of the micro-orifice [300] constrain the
cell(s) and the cells take on the shape of the micro-orifice [300], e.g., circular. A test agent is
applied through the micro-orifices [300] and is allowed to contact the cells. The first layer
(surface) [150] is removed and the cells are observed. If the test agent affects cell movement, the
cell will be "stuck" in place as-it was patterned and-may not change shape, i.e., it will remain
circular if the patterning member had circular orifices. On the other hand, if the test agent does
not effect cell movement, the cell will move away from its original patterned position and change
shape from the patterned circular shape since the constraints of the first layer [150] had been
removed. As interpreted by the examiner, BCim teaches cell migration after being contacted by
[150].

In light of the cancelation of claim 13 and amendment of claim 91, the 112 2nd paragraph
rejections have been withdrawn.

Claim Objections

Claims 22, 27, 109, and 111 are objected to under 37 CFR 1.75(c), as being of improper
dependent form for failing to fiirther limit the subject matter of a previous claim. Applicant is

Application/Control Number: 1 0/561 ,839 Page 4

Art Unit: 1797

required to cancel the claim(s), or amend the claim(s) to place the claim(s) in proper dependent
form, or rewrite the claim(s) in independent form.

Regarding claims 22, 27, 109, and 1 1 1, the claims fail to further limit the structure of the
device as claimed.

Claim Rejections - 35 USC § 112
The following is a quotation of the second paragraph of 35 U.S.C. 1 12:

The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the
subject matter which the applicant regards as his invention.

Claims 43 and 48 are rejected under 35 U.S.C. 1 12, second paragraph, as being indefinite
for failing to particularly point out and distinctly claim the subject matter which applicant

regards as the invention.

Regarding Claim 43, "the interwell area" has not been defined by any dimension and is
therefore indefinite.

Regarding Claim 48, the examiner is unclear as to what and how knife-edge defines the
well structure.

Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the
basis for the rejections under this section made in this Office action:

A person shall be entitled to a patent unless -

(a) the invention was known or used by others in this country, or patented or described in a printed publication in this
or a foreign country, before the invention thereof by the applicant for a patent.

Application/Control Number: 10/561,839
Art Unit: 1797

Page 5

(b) the invention was patented or described in a printed publication in this or a foreign country or in pubhc use or on
sale in this country, more than one year prior to the date of apphcation for patent in the United States.

Claims 1-2, 5, 42, 80, 86, 145, 153, and 156 are rejected under 35 U.S.C. 102(b) as being
anticipated by Bochner et al. (US 5627045).

Regarding Claims 1 and 5, 42, 80, and 86, Bochner et al. ('045) teaches a device for
holding living cells, the device comprising a carrier [ICQ] having a plurality of juxtaposed wells
[130] disposed on a surface [120] each well configured to hold at least one living cell, the device
characterized in that the insides of said wells are configured to or formed to inhibit adhesion of
living cells held in said wells (Col 8, line 35-Col 9, line 9 and Figures 1-4).

Regarding Claim 2, Bochner et al. ('045) teaches wherein the inside of said wells
comprises a material selected from the group consisting of a gel (Col 8, line 65-Col 9, line 9).

Regarding Claim 145, Bochner et al. ('045) teaches method of making a chip-device
comprising: providing a carrier having a plurality of wells disposed on a surface,
each well configured to hold at least one living cell; and coating the inside of said wells with a
layer of a material configured to infiuence proliferation of living cells held in said wells (Col 8,
line 65-Col 9, line 34; Example 4).

Regarding Claims 153 and 156, Bochner et al. ('045) teaches a method of manipulating
cells, comprising: providing a plurality of wells of a well-bearing component, each well
configured to hold at least one living cell; holding a plurality of living cells in a plurality of said

Application/Control Number: 1 0/561 ,839 Page 6

Art Unit: 1797

wells; placing a gellable fluid in proximity with said surface so as to fill said plurality of wells;
and gelling said gellable fluid so as to form a gel cover (Col 8, line 65-Col 9, line 34).

The examiner interprets the gel matrix of Bochner to be a cover once produced, trapping
the suspended microorganisms.

Claims 1-3, 5-7, 35, 42-43, 49, 68, 74, 86, 121, 130, 132, 139, 145, 186 and 193 are
rejected under 35 U.S.C. 102(a) as being anticipated by Kim et al. (US 20030030184).

Regarding Claims 1, 5, 42, 86, Kim et al. ('184) teaches a device for holding living cells,
the device comprising a carrier [100] having a plurality of juxtaposed wells [170] disposed on a
surface [140] each well configured to hold at least one living cell, the device characterized in that
said wells are configured to influence the proliferation of living cells held in said wells
(Paragraphs 135 and 215 and Figures 1).

Regarding Claims 2-3, Kim et al. ('184) teaches wherein said carrier is substantially
made of a material selected from the group consisting of a polydimethylsiloxane, an elastomer
and silicon rubber (Paragraphs 138 and 143).

Regarding Claims 6-7, Kim et al. ('184) teaches wherein the carrier can be formed by
molding (Paragraph 194). Therefor the device is capable of deforming in at least one dimension
and changing the size of the wells.

Application/Control Number: 1 0/561 ,839 Page 7

Art Unit: 1797

Regarding Claim 35, Kim et al. ('184) teaches wherein the inside of said wells is
configured to delay adhesion of living cells thereto (Paragraph 214).

Regarding Claims 43 and 49, Kim et al. ('184) teaches wherein the dimensions of said
wells are less than about 200 microns (Paragraph 142).

Regarding Claim 68, Kim et al. ('184) teaches protuberances protruding from said
surface between two adjacent wells (Paragraph 135; Figures lb: 160a; lb: 150a).

Regarding Claim 74, Kim et al. ('184) teaches at least one wall protruding from said
surface, said at least one wall circumscribing at least one area of said surface where the points of
the top edge of said wall define a plane (Figures 1 and lb).

Regarding Claim 86, Kim et al. ('184) teaches a carrier comprising a first layer [150] of a
first material resting on top of a second layer [160] of a second material, the carrier having a
plurality of wells [170] disposed on an upper surface of said first layer each of said plurality of
wells configured to hold at least one living cell, wherein the bottom of said plurality of wells is
said second layer (Paragraph 132 and Figiires 1,1a and 2a).

Regarding Claims 121, 130, 132 and 139, Kim et al. ('184) teaches a method of making a
chip-device of claim 1 comprising: providing a template having a negative of features of said
surface of said carrier; contacting said template with a precursor material so as to create said

Application/Control Number: 1 0/561 ,839 Page 8

Art Unit: 1797

features in said precursor material; and fixing said features in said precursor material so as to
fashion said carrier (Paragraphs 190-199).

PDMS is viscoelastic, meaning that at long flow times (or high temperatures), it acts like
a viscous liquid, similar to honey (of which the examiner interprets to be the same as a gellable
fluid) which can flow to cover the surface and mold to any surface imperfections. However at
short flow times (or low temperatures) it acts like an elastic solid, similar to rubber.

Regarding Claim 145, Kim et al. ('184) teaches a method of making a chip-device
comprising: providing a carrier having a plurality of wells disposed on a surface,
each well configured to hold at least one living cell; and coating the inside of said wells with a
layer of a material configured to influence proliferation of living cells held in said wells
(Paragraphs 135, 206, and 215).

Regarding Claim 186, Kim et al. ('184) teaches a method of growing cells comprising:
providing a well-bearing device; holding at least one living cell in a well of said well-bearing
device (Figure 1); and increasing the size of said well so as to provide an increased space for
proliferation of said cell (Paragraph 208).

Regarding Claim 193, Kim et al. ('184) teaches a method comprising: providing a well-
bearing device, said well-bearing device having: a plurality of wells disposed on a surface, each
well configured to hold at least one cell; and a plurality of protuberances protruding from said

Application/Control Number: 1 0/561 ,839 Page 9

Art Unit: 1797

surface contacting the biological sample with said surface so as to remove cells from the
biological sample (Paragraphs 135, 208 and Figures 1 and lb).

Claim Rejections - 35 USC § 103

The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all

obviousness rejections set forth in this Office action:

(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in
section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are
such that the subject matter as a whole would have been obvious at the time the invention was made to a person
having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the
manner in which the invention was made.

The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459
(1966), that are applied for establishing a background for determining obviousness under 35
U.S.C. 103(a) are summarized as follows:

1 . Determining the scope and contents of the prior art.

2. Ascertaining the differences between the prior art and the claims at issue.

3. Resolving the level of ordinary skill in the pertinent art.

4. Considering objective evidence present in the application indicating obviousness
or nonobviousness.

This application currently names joint inventors. In considering patentability of the
claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various
claims was commonly owned at the time any inventions covered therein were made absent any
evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1 .56 to point out

Application/Control Number: 1 0/561 ,839 Page 1 0

Art Unit: 1797

the inventor and invention dates of each claim that was not commonly owned at the time a later
invention was made in order for the examiner to consider the applicability of 35 U.S. C. 103(c)
and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).

Claims 12 and 90-91 are rejected under 35 U.S.C. 103(a) as being unpatentable over Kim
et al. (US 20030030184) as applied above to claim 1, further in light of Sanghera et al. (US
5525800) and Hahn et al. (US 20030017079).

Regarding Claims 12 and 90, Kim et al. ('184) teaches a chip-device for holding living
cells, the device comprising a carrier [100] having a plurality of wells [170] disposed on a
surface each well configured to hold at least one living cell, the device characterized in that said
carrier is made of PDMS, a material having an index of refi-action similar to that of water
(Paragraphs 138 and 143).

PDMS is well known on the art to have a refi^active index of about 1 .4 as evidenced by
Sanghera et al. in Col 8, lines 54-56 which is close to the refi-active index of water which is equal
to 1.33 as evidenced by Hahn et al. in Paragraph 19.

Regarding Claim 91 Kim et al. ('184) teaches a chip-device for holding living cells, the
device comprising a carrier [100] having a plurality of wells [170] disposed on a surface each
well configured to hold at least one living cell, the device characterized in that said carrier is
made of a material having an index of refraction similar to that of water (Paragraphs 138 and
143).

Application/Control Number: 1 0/561 ,839 Page 1 1

Art Unit: 1797

PDMS is well known on the art to have a refractive index of about 1 .4 as evidenced by
Sanghera et al. in Col 8, lines 54-56 which is close to the refractive index of water which is equal
to 1.33 as evidenced by Hahn et al. in Paragraph 19.

It would have been obvious to one having ordinary skill in the art at the time the
invention was made to modify Kim with a material having an index of refraction less than about
1 .4, in order to optimize the carriers ability to identify the particular living cell, confirm its purity
or measure its concenfration via the use of an optical system.

Claims 18, 22, 27, 29-30, 105, 109, and 1 11 are rejected under 35 U.S.C. 103(a) as being
unpatentable over Kim et al. (US 20030030184) as apphed above to claim 1, further in view of
Ravkin et al. (US 2003/0059764).

Regarding Claims 18, 22, 27, and 29-30, Kim et al. ('184) teaches the device of claim 1
except for wherein the carrier and cover are made of gel.

Ravkin ('764) teaches a cell analysis system wherein carriers or portions thereof, such as
an outer layer (cover) or an internal region also may be made from a gel (Paragraph 90).

The examiner interprets the outer layer described by Ravkin to be equivalent to a cover.

It would have been obvious to one having ordinary skill in the art at the time the
invention was made to modify Kim with gel portion as taught by Ravkin in order to provide a
suitable adhesion layer for cells and cell analysis materials or provide a better storage or
handling characteristics.

With respect to the intended use limitations, the device disclosed by Kim and Ravkin is
structurally the same as the instantly claimed and is capable of providing the operating

Application/Control Number: 1 0/561 ,839 Page 1 2

Art Unit: 1797

conditions listed in the intended use section of the claim. Note statements of intended use carry
no patentable weight when the structure of the Claim has been met by the prior art reference.

Regarding Claims 105, 109, and 111, Kim et al. ('184) teaches a device for holding living
cells, the device comprising a carrier [100] having a plurality of juxtaposed wells [170] disposed
on a surface [140] each well configured to hold at least one living cell, the device characterized
in that said wells are configured to influence the proliferation of living cells held in said wells
(Paragraphs 135 and 215 and Figures 1). Kim also discloses wherein the device comprises at
least one cover (Paragraph 28).

Kim does not disclose wherein the said cover is made of gel.

Ravkin ('764) teaches a cell analysis system wherein carriers or portions thereof, such as
an outer layer (cover) or an internal region also may be made from a gel (Paragraph 90).

The examiner interprets the outer layer described by Ravkin to be equivalent to a cover.

It would have been obvious to one having ordinary skill in the art at the time the
invention was made to modify Kim with gel portion as taught by Ravkin in order to provide a
suitable adhesion layer for cells and cell analysis materials or provide a better storage or
handling characteristics.

With respect to the intended use limitations, the device disclosed by Kim and Ravkin is
structurally the same as the instantly claimed and is capable of providing the operating
conditions listed in the intended use section of the claim. Note statements of intended use carry
no patentable weight when the structure of the Claim has been met by the prior art reference.

Application/Control Number: 1 0/561 ,839 Page 1 3

Art Unit: 1797

Claims 178-179 and 181 are rejected under 35 U.S.C. 103(a) as being unpatentable over
Bochner et al. (US 5627045) as applied above to claim 153, further in view of Kim et al. (US
20030030184).

Regarding Claims 178-179 and 181, Bochner ('045) teaches the method of claim 153 as
rejected above except for isolating at least one cell by excising said at least
one said cell from said well-bearing component and contacting an active entity-containing fluid
with said gel cover.

Kim ('184) teaches contacting an active entity-containing fluid with the well bearing
device (Paragraph 205, 208 and 214). Kim also teaches wherein the cells were removed from the
macro-wells (Paragraph 293).

It would have been obvious to one having ordinary skill in the art at the time the
invention was made to modify Bochner with the method of adding a test solution/agent as taught
by BCim in order to provide a method of identifying microbes, methods of screening for the
activity of drugs, methods for detecting toxic substances and methods for detecting intercellular
reactions.

Application/Control Number: 1 0/561 ,839 Page 1 4

Art Unit: 1797

Conclusion

THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time
policy as set forth in 37 CFR 1.136(a).

A shortened statutory period for reply to this final action is set to expire THREE
MONTHS from the mailing date of this action. In the event a first reply is filed within TWO
MONTHS of the mailing date of this final action and the advisory action is not mailed until after
the end of the THREE-MONTH shortened statutory period, then the shortened statutory period
will expire on the date the advisory action is mailed, and any extension fee pursuant to 37
CFR 1 .136(a) will be calculated from the mailing date of the advisory action. In no event,
however, will the statutory period for reply expire later than SIX MONTHS from the mailing
date of this final action.

Any inquiry concerning this communication or earlier communications fi-om the
examiner should be directed to LYDIA EDWARDS whose telephone number is (571)270-3242.
The examiner can normally be reached on Mon-Thur 6:30-5:00.

If attempts to reach the examiner by telephone are unsuccessfiil, the examiner's
supervisor, Walter Griffin can be reached on 571.272.1447. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300.

Application/Control Number: 1 0/561 ,839 Page 1 5

Art Unit: 1797

Information regarding the status of an application may be obtained from the Patent
Application Information Retrieval (PAIR) system. Status information for published appUcations
may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
applications is available through Private PAIR only. For more information about the PAIR
system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would
like assistance from a USPTO Customer Service Representative or access to the automated
information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.

/LYDIA EDWARDS/

Examiner

Art Unit 1797

LE

/Walter D. Griffin/

Supervisory Patent Examiner, Art Unit 1797